Project 1: Assessing MRI Biomarkers of White Matter Injury Due to the different pathologies and sub-optimal responses to existing therapies, there is a great need for more accurate and noninvasive methods to determine MS disease activity and pathologic subtype in living humans. This need is particularly acute when examining potential new therapies for MS14. In the Project 1 of this PPG, two degrees of severity of experimental autoimmune encephalomyelitis (EAE) will be examined using in vivo DTI and various histological staining of axon and myelin integrity to establish a definitive correspondence between the underlying pathologies and DTI biomarkers and histology stains. In this proposed Project 1, DTI biomarkers will be used as a marker of disease severity that reflects underlying pathology and predicts clinical outcome independent of treatment15, to evaluate the therapeutic efficacy of NBQX16'17 on optic nerves and spinal cords from mice of EAE as well as to test the prognostic significance in longitudinal history studies in a EAE mice.